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强迫肢体使用可增强老年大鼠中风后的神经发生及行为恢复。

Forced limb-use enhanced neurogenesis and behavioral recovery after stroke in the aged rats.

作者信息

Qu H L, Zhao M, Zhao S S, Xiao T, Song C G, Cao Y P, Jolkkonen J, Zhao C S

机构信息

Neurology, The First Hospital of China Medical University, Shenyang, China.

Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Neuroscience. 2015 Feb 12;286:316-24. doi: 10.1016/j.neuroscience.2014.11.040. Epub 2014 Nov 26.

Abstract

Constraint-induced movement therapy (CIMT) after stroke enhances not only functional reorganization but also structural plasticity of the brain in the adult rats. We examined whether forced limb-use which mimicked CIMT could influence ischemia-induced neurogenesis, apoptosis and behavioral recovery in the aged rats. Aged rats were divided into a sham group, an ischemia group, and an ischemia group with forced limb-use. Focal cerebral ischemia was induced by injection of endothelin-1. Forced limb-use began on post-stroke day 7 by fitting a plaster cast around the unimpaired upper limbs of rats for 3 weeks. Behavioral recovery was evaluated by tapered/ledged beam-walking test on postoperative day 32. The expression of doublecortin, neuronal nuclei, glial fibrillary acidic protein and Iba-1 were measured by single or double immunohistochemistry, and apoptosis was measured by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. The production of neuroblasts in the subventricular zone (SVZ) was significantly increased after stroke. Forced limb-use enhanced the proliferation of newborn neurons in the SVZ, as well as increased the long-term survival of newborn neurons. Furthermore, forced limb-use suppressed apoptosis and improved the motor functions after stroke in the aged rats. Forced limb-use exerted few effects on inflammation. Neither the number nor dendritic complexity of newborn granule cells in the hippocampus was affected by forced limb-use. Forced limb-use is effective in enhancing neurogenesis and behavioral recovery after stroke even in the aged rats.

摘要

中风后强制使用肢体疗法(CIMT)不仅能增强成年大鼠大脑的功能重组,还能增强其结构可塑性。我们研究了模拟CIMT的强制肢体使用是否会影响老年大鼠缺血诱导的神经发生、细胞凋亡和行为恢复。将老年大鼠分为假手术组、缺血组和缺血后强制肢体使用组。通过注射内皮素-1诱导局灶性脑缺血。中风后第7天开始强制肢体使用,给大鼠未受损的上肢戴上石膏绷带,持续3周。术后第32天通过锥形/带壁梁行走试验评估行为恢复情况。通过单免疫组化或双免疫组化检测双皮质素、神经元细胞核、胶质纤维酸性蛋白和离子钙结合衔接分子-1的表达,并通过TdT介导的dUTP生物素缺口末端标记(TUNEL)法检测细胞凋亡。中风后室下区(SVZ)神经母细胞的产生显著增加。强制肢体使用增强了SVZ新生神经元的增殖,同时增加了新生神经元的长期存活率。此外,强制肢体使用抑制了细胞凋亡,并改善了老年大鼠中风后的运动功能。强制肢体使用对炎症影响较小。强制肢体使用对海马中新生颗粒细胞的数量和树突复杂性均无影响。即使在老年大鼠中,强制肢体使用对增强中风后的神经发生和行为恢复也有效。

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